Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-4 (of 4 Records) |
Query Trace: Majer M[original query] |
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In silico toxicology protocols.
Myatt GJ , Ahlberg E , Akahori Y , Allen D , Amberg A , Anger LT , Aptula A , Auerbach S , Beilke L , Bellion P , Benigni R , Bercu J , Booth ED , Bower D , Brigo A , Burden N , Cammerer Z , Cronin MTD , Cross KP , Custer L , Dettwiler M , Dobo K , Ford KA , Fortin MC , Gad-McDonald SE , Gellatly N , Gervais V , Glover KP , Glowienke S , Van Gompel J , Gutsell S , Hardy B , Harvey JS , Hillegass J , Honma M , Hsieh JH , Hsu CW , Hughes K , Johnson C , Jolly R , Jones D , Kemper R , Kenyon MO , Kim MT , Kruhlak NL , Kulkarni SA , Kümmerer K , Leavitt P , Majer B , Masten S , Miller S , Moser J , Mumtaz M , Muster W , Neilson L , Oprea TI , Patlewicz G , Paulino A , Lo Piparo E , Powley M , Quigley DP , Reddy MV , Richarz AN , Ruiz P , Schilter B , Serafimova R , Simpson W , Stavitskaya L , Stidl R , Suarez-Rodriguez D , Szabo DT , Teasdale A , Trejo-Martin A , Valentin JP , Vuorinen A , Wall BA , Watts P , White AT , Wichard J , Witt KL , Woolley A , Woolley D , Zwickl C , Hasselgren C . Regul Toxicol Pharmacol 2018 96 1-17 The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates the information needed for protocols to support in silico predictions for major toxicological endpoints of concern (e.g., genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity) across several industries and regulatory bodies. Such novel in silico toxicology (IST) protocols, when fully developed and implemented, will ensure in silico toxicological assessments are performed and evaluated in a consistent, reproducible, and well-documented manner across industries and regulatory bodies to support wider uptake and acceptance of the approaches. The development of IST protocols is an initiative developed through a collaboration among an international consortium to reflect the state-of-the-art in in silico toxicology for hazard identification and characterization. A general outline for describing the development of such protocols is included and it is based on in silico predictions and/or available experimental data for a defined series of relevant toxicological effects or mechanisms. The publication presents a novel approach for determining the reliability of in silico predictions alongside experimental data. In addition, we discuss how to determine the level of confidence in the assessment based on the relevance and reliability of the information. |
Operational challenges and considerations for COVID-19 research in humanitarian settings: A qualitative study of a project in Eastern Democratic Republic of the Congo and South Sudan.
Majer J , Udoh K , Beleke A , Ahmed D , Kumar D , Summers A , Ververs M , Bollemeijer I , Doocy S . PLoS One 2022 17 (6) e0267822 Since the beginning of the COVID-19 pandemic, much research has been conducted globally, but relatively few studies have been carried out in complex emergency settings that pose numerous operational challenges. We conducted a qualitative study to explore the barriers and enablers of a COVID-19 cohort study conducted in South Sudan and Eastern Democratic Republic of the Congo, to inform future research on COVID-19 and infectious diseases in humanitarian settings. We used a case study design embedded within the original prospective cohort study. Qualitative data was collected through four health facility assessments, 28 key informant interviews, and a focus group discussion. Data were analyzed using a manual thematic analysis approach and summarized against four primary themes: testing challenges and enablers, perceptions and attitudes towards COVID-19, national health system considerations, and study management considerations. Findings suggest most of the challenges affecting the cohort study were not specific to COVID-19 research but have been a feature of previous infectious disease research carried out in complex emergencies. However, the pandemic has exacerbated certain problems. The high proportion of travellers enrolled due to testing mandates, stigmatization of infected individuals linked to the heavy global focus on COVID-19, strained resources during waves of increasing infections, and remote management requirements all negatively impacted the cohort study. Factors that facilitated the research included proactive management, data quality oversight procedures, and strong collaboration with national health stakeholders. The global impact of COVID-19, its high public profile, and specific pandemic policies pose further operational challenges for research in already complex humanitarian settings. Future studies could plan mitigation measures that include flexibility in staffing and budgets, strategies to expand testing, and early partnerships with local organizations and health authorities. |
Risk factors for hospitalisation and death from COVID-19: a prospective cohort study in South Sudan and Eastern Democratic Republic of the Congo.
Leidman E , Doocy S , Heymsfield G , Sebushishe A , Mbong EN , Majer J , Bollemeijer I . BMJ Open 2022 12 (5) e060639 OBJECTIVES: Our study described demographic characteristics, exposures and symptoms, and comorbidities to evaluate risk factors of hospitalisation and mortality among cases in Juba, South Sudan (SSD) and North and South Kivu in eastern Democratic Republic of the Congo (DRC). DESIGN: Prospective observational cohort of COVID-19 cases. METHODS: Individuals presenting for care at one of five study facilities in SSD (n=1) or DRC (n=4) or referred from home-based care by mobile medical teams between December 2020 and June 2021 were eligible for enrolment. Demographic characteristics, COVID-19 exposures, symptoms at presentation, as well as acute and chronic comorbidities, were evaluated using a standard questionnaire at enrolment. Disease progression was characterised by location of care using mixed-effects regression models. RESULTS: 751 individuals were eligible for enrolment. Among cases followed to discharge or death (n=519), 375 were enrolled outpatients (75.7%). A similar number of cases were enrolled in DRC (n=262) and SSD (n=257). Overall mortality was 4.8% (95% CI: 3.2% to 6.9%); there were no outpatient deaths. Patients presenting with any symptoms had higher odds of hospitalisation (adjusted OR (AOR) 2.78, 95% CI 1.47 to 5.27) and all deaths occurred among symptomatic individuals. Odds of both hospitalisation and mortality were greatest among cases with respiratory symptoms; presence of low oxygen levels on enrolment was strongly associated with both hospitalisation (AOR 7.77, 95% CI 4.22 to 14.29) and mortality (AOR 25.29, 95% CI 6.42 to 99.54). Presence of more than one chronic comorbidity was associated with 4.96 (95% CI 1.51 to 16.31) times greater odds of death; neither infectious comorbidities evaluated, nor malnutrition, were significantly associated with increased mortality. CONCLUSIONS: Consistent with prior literature, older age, low oxygen level, other respiratory symptoms and chronic comorbidities were all risk factors for mortality. Patients presenting with these characteristics were more likely to be hospitalised, providing evidence of effective triage and referral. TRIAL REGISTRATION NUMBER: NCT04568499. |
Association of childhood trauma with cognitive function in healthy adults: a pilot study
Majer M , Nater UM , Lin JM , Capuron L , Reeves WC . BMC Neurol 2010 10 61 BACKGROUND: Animal and human studies suggest that stress experienced early in life has detrimental consequences on brain development, including brain regions involved in cognitive function. Cognitive changes are cardinal features of depression and posttraumatic stress disorder. Early-life trauma is a major risk factor for these disorders. Only few studies have measured the long-term consequences of childhood trauma on cognitive function in healthy adults. METHODS: In this pilot study, we investigated the relationship between childhood trauma exposure and cognitive function in 47 healthy adults, who were identified as part of a larger study from the general population in Wichita, KS. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the Wide-Range-Achievement-Test (WRAT-3) to examine cognitive function and individual achievement. Type and severity of childhood trauma was assessed by the Childhood Trauma Questionnaire (CTQ). Data were analyzed using multiple linear regression on CANTAB measures with primary predictors (CTQ scales) and potential confounders (age, sex, education, income). RESULTS: Specific CTQ scales were significantly associated with measures of cognitive function. Emotional abuse was associated with impaired spatial working memory performance. Physical neglect correlated with impaired spatial working memory and pattern recognition memory. Sexual abuse and physical neglect were negatively associated with WRAT-3 scores. However, the association did not reach the significance level of p < 0.01. CONCLUSIONS: Our results suggest that physical neglect and emotional abuse might be associated with memory deficits in adulthood, which in turn might pose a risk factor for the development of psychopathology. |
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